Mercury and Neurodevelopmental Toxicity in Children

This article reviews the current scientific evidence on mercury and adverse neurodevelopmental effects on children. Methyl mercury readily crosses the placenta and the blood brain barrier and is known to be neurotoxic. High dose prenatal exposure to methyl mercury causes mental retardation and cerebral palsy. Lower levels from maternal consumption of fish have been associated with adverse neurodevelopmental outcomes in some studies but not in others. Two large longitudinal cohort studies are currently underway, one in the Seychelles where fish consumption is quite high, and one in the Faroe Islands where people consume whale meat and fish. The Seychelles children have not demonstrated adverse neurodevelopmental effects that correlate with maternal hair mercury levels, whereas the children in the Faroe Islands have shown deficits in learning and memory that correlate with cord-blood mercury levels.

This is the most recent study based on the cohort of 1,022 children born in the Faroe Islands in 1986-87. Intrauterine methyl mercury exposure was determined from mercury concentrations in cord blood and 2 sets of maternal hair. Neurobehavioral performance of 917 children (90 percent) was assessed at age 7. In children with complete exposure data, 8 of 16 neuropsychological tests showed deficits significantly associated with the cord-blood mercury concentration after confounder adjustment. The study supports previous findings from this cohort study that maternal mercury exposure during pregnancy is associated with neuropsychological deficits detectable at age 7 years.

This is the most recent study based on the cohort of 779 children enrolled at 6 months of age in the Republic of Seychelles in 1989-90. Intrauterine mercury exposure was estimated by collecting maternal hair that would have been growing during pregnancy. Neurobehavioral performance was assessed at age 9 years. Most endpoints showed no association with mercury concentration in maternal hair. There was an association with decreased performance in the grooved pegboard test in the non-dominant hand in males, and with slightly improved scores in the hyperactivity index. This study supports previous findings for this cohort that did not find significant associations between maternal hair mercury levels during pregnancy and subsequent neurobehavioral performance of children. These results are quite different than those found in the Faroe Islands cohort.

This case-control study, conducted in eight European countries and Israel, evaluated the association of mercury levels in toenail clippings and docosahexaenoic acid (DHA) levels in adipose tissue with the risk of a first myocardial infarction among men. The study included 684 men with a first diagnosis of myocardial infarction and 724 controls. After adjustment for the DHA level and coronary risk factors, the mercury levels in the patients were 15 percent higher than those in controls. The risk-factor-adjusted odds ratio for myocardial infarction associated with the highest as compared with the lowest quintile of mercury was 2.16 (95 percent confidence interval, 1.09 to 4.29; P for trend=0.006). The toenail mercury level was directly associated with the risk of myocardial infarction. The authors concluded that high mercury content may diminish the cardioprotective effect of fish intake.

This study used a nested case-control design to investigate the association between mercury levels in toenails and the risk of coronary heart disease among a cohort of 33,737 male health professionals with no previous history of cardiovascular disease or cancer who were 40 to 75 years of age in 1986. During five years of follow-up, there were 470 cases of coronary-artery surgery, nonfatal myocardial infarction, and fatal coronary heart disease. Each patient was matched according to age and smoking status with a control subject. The mercury level was significantly correlated with fish consumption (Spearman r=0.42, P<0.001), and the mean mercury level was higher in dentists than in nondentists (mean, 0.91 and 0.45 microg per gram, respectively; P<0.001). After age, smoking, and other risk factors for coronary heart disease had been controlled for, the mercury level was not significantly associated with the risk of coronary heart disease. Adjustment for intake of n-3 fatty acids from fish did not change these results. The authors concluded that these findings do not support an association between total mercury exposure and the risk of coronary heart disease, but a weak relation cannot be ruled out.

Although previous studies have suggested an association between high fish intake and reduced coronary heart disease (CHD) mortality, men in Eastern Finland, who have a high fish intake, have an exceptionally high CHD mortality. The authors hypothesized that this paradox could be in part explained by high mercury content in fish. 1,833 men aged 42 to 60 years who were free of clinical CHD, stroke, claudication, and cancer were recruited into a cohort for study. Of these, 73 experienced an acute myocardial infarction (AMI) in 2 to 7 years. Men who had consumed local nonfatty fish species had elevated hair mercury contents. In Cox models with the major cardiovascular risk factors as covariates, dietary intakes of fish and mercury were associated with significantly increased risk of AMI and death from CHD, CVD, and any death. Men in the highest tertile (> or = 2.0 micrograms/g) of hair mercury content had a 2.0-fold (95 percent confidence interval, 1.2 to 3.1; P = .005) age- and CHD-adjusted risk of AMI and a 2.9-fold (95 percent CI, 1.2 to 6.6; P = .014) adjusted risk of cardiovascular death compared with those with a lower hair mercury content. In a nested case-control subsample, the 24-hour urinary mercury excretion had a significant (P = .042) independent association with the risk of AMI. Both the hair and urinary mercury associated significantly with titers of immune complexes containing oxidized LDL. The authors concluded that these data suggest that a high intake of mercury is associated with an excess risk of AMI as well as death from CHD, CVD, and any cause in Eastern Finnish men and this increased risk may be due to the promotion of lipid peroxidation by mercury.

Mercury Exposure in the U.S. Population

This study reported on the 1999-2000 data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional survey of the noninstitutionalized US population. The NHANES included 1,250 children aged 1 to 5 years and 2,314 women aged 16 to 49 years. Household interviews, physical examinations, and blood mercury levels assessments were performed on 705 children and 1,709 women. Blood mercury levels were approximately 3-fold higher in women compared with children. The geometric mean concentration of total blood mercury was 0.34 micro g/L (95 percent confidence interval [CI], 0.30-0.39 microg/L) in children and 1.02 microg/L (95 percent CI, 0.85-1.20 microg/L) in women. Geometric mean mercury levels were almost 4-fold higher among women who ate 3 or more servings of fish in the past 30 days compared with women who ate no fish in that period. Approximately 8 percent of women had concentrations of mercury in their blood higher than the US Environmental Protection Agency's recommended reference dose below which exposures are considered to be without adverse effects.

All 720 patients in a 1-year period who came for an office visit to an internal medicine practice in San Francisco, California, were evaluated for mercury excess. On the basis of questionnaire results indicating significant fish consumption, 123 patients underwent blood testing. Mercury levels in this subgroup ranged from 2.0 to 89.5 micro g/L. The mean for women was 15 micro g/L [standard deviation (SD) = 15], and for men was 13 micro g/L (SD = 5); 89 percent had levels exceeding the RfD. Subjects consumed 30 different types of fish. Swordfish had the highest correlation with mercury level. The U.S. Environmental Protection Agency (U.S. EPA) and the National Academy of Sciences recommend keeping the whole blood mercury level < 5.0 micro g/L. The mean level for women in this survey was 10 times that found in the recent NHANES survey.

Mercury Regulations

Rice DC, Schoeny R, Mahaffey K. "Methods and rationale for derivation of a reference dose for methyl mercury by the U.S. EPA." in Risk Anal, 23(1), 2003, pp. 107-15.

In 2001, the U.S. Environmental Protection Agency derived a reference dose (RfD) for methyl mercury, which is a daily intake that is likely to be without appreciable risk of deleterious effects during a lifetime. This derivation used a series of benchmark dose (BMD) analyses provided by a National Research Council (NRC) panel convened to assess the health effects of methyl mercury. Analyses were performed for a number of endpoints from three large longitudinal cohort studies of the neuropsychological consequences of in utero exposure to methyl mercury: the Faroe Islands, Seychelles Islands, and New Zealand studies. Adverse effects were identified in the Faroe Islands and New Zealand studies, but not in the Seychelles Islands. The EPA applied a total uncertainty factor (UF) of 10 for intrahuman toxicokinetic and toxicodynamic variability and uncertainty. Derivation of potential RfDs from a number of endpoints from the Faroe Islands study converged on 0.1 microg/kg/day, as did the integrative analysis of all three studies.